In MEMS (micro electro mechanical systems) or micro systems technology (MST), sensors and actuators have been developed based on micro-cantilever technology wherein mechanical conversion of chemical or biomolecular events is employed. For example, it has been reported that a thin micro-cantilever bends due to surface stress change caused by a specific biomolecular reaction such as DNA hybridization. In addition, a thin film of gold foil has been demonstrated to change its length due to an ionic adsorption by surface stress induced by an electrochemical reaction.
There are advantages enabled by this micro-cantilever approach over conventional dye and other sensing methods. In micro-cantilever technology, for example, a biomolecular reaction can be detected without tagging molecules with optically observable chemicals such as dye or fluorescent particles. It is also considered possible that many micro-cantilevers can be coated with different-chemical binding-sites in order to obtain multiple answers with single testing. It may also be possible that many micro-cantilevers can be coated with different chemical binding sites and multiple detection can be made for one sample introduced to react with different micro-cantilevers. There are, however, certain difficulties and limits of this micro-cantilever based method as listed below; namely:    Detection limit    Cost of detection    Detection time    Multiple detections    Linearity and dynamic range
Detection limit: The amount of cantilever bending is extremely small, in the range of 10–100 nm. A sensing method such as optical detection that can resolve a fraction of a nanometer is required. Nevertheless, the best detection limit of the method is above 10 nM range in biomolecular concentration according to literature. In contrast, optical detection based on light sensitive particles such as laser induced fluorescence can sense 1 pM range. Use of soft material such as SU-8 plastic cantilever, was considered to improve the detection limit problem. The thickness of the plastic cantilever beam, however, had to be increased, and this approach resulted in a poor detection limit. Even if a thinner plastic cantilever structure is used for better detection limit, the cantilever structure will be too flexible to maintain its shape in a fluid.
Cost of detection: An optical detection method needs to be used to maintain the detection limit of existing approaches. A laser source based detection system is be integrated with the micro-cantilever samples. The overall system becomes bulky and complicated in this case. Multiple laser sources are needed for multiple detection, adding to the cost and complexity. Furthermore, this system cannot be used with optically non-transparent solutions such as blood. Piezoresistive elements can be integrated with the micro-cantilevers in order to overcome the problems mentioned here. However, the detection limit by this method is even worse compared to conventional methods such as optical detection.
Detection time: Flexible micro-cantilevers submerged in a liquid solution will undergo a significant fluctuation in their shapes due to very small fluid disturbance. Accordingly, a sufficient time is needed for settling down the fluctuation. Introduction of the sample for detection needs to be done with extreme care, and the sample solution is injected from some distance from the cantilevers. The reaction time afterwards is strictly limited by diffusion of molecules to the cantilevers. This process without any help of mixing flow is very slow and inefficient. As a result, it takes very long for a typical detection, on the order of hours.
Multiple detection: One of the major advantages claimed by the use of micro-cantilevers is the possibility of detecting many reactions with one analyte solution. To achieve this goal, it is required to fabricate many cantilevers in a batch fashion. This has been achieved by using photolithography-based microfabrication. It is also important to coat different beams with different molecules to obtain multiplexed reaction signals. The coating process, however, is extremely difficult with any of the present methods when many cantilevers (e.g., hundreds) are required to be coated with different molecules. Photolithography-based synthesis of molecules (e.g., Affimetrix approach) are difficult to carry out because the completed cantilever structures are too flexible. Various kinds of stamping techniques (e.g., Cartesian DNA microarray) cannot be used for this same reason because the flexible cantilevers will be attached on the substrate after the solution is dried. Use of multiple light source also limits the number of detectable cantilevers available. It would be an extremely difficult and time consuming task to integrate and calibrate many laser light sources.